A family study of primary affective disorders is being performed. Biologic characteristics of the patients are evaluated for usefulness as genetic markers of vulnerability to affective disorders. Platelet monoamine oxidase is not a marker of vulnerability within pedigrees, although it is associated with increased risk of illness in relatives. Genetic linkage of affective disorders to known chromosomal markers is also studied. Histocompatibility Leukocyte Antigens (HLA) are not associated with Bipolar affective illness and are not markers of vulnerability within pedigrees. Study of specific genes in pedigrees revealed a previously undocumented gene, a null allele for esterase D. Dopamine beta hydroxylase (DBH) is not transmitted as an autosomal recessive. Heterozygosity for phenylketonuria (PKU) is not increased among bipolar patients. Mathematical models of genetic transmission have been developed for application to these data. Clinical applications of genetic findings to prediction of pharmacologic response, case finding in the population, and genetic counseling have been developed.